Transplantation of oligodendrocytes (i.e., oligodendroglia) (Archer D. R., et al., 1994. Exp. Neurol. 125:268-77; Blakemore W. F., Crang A. J., 1988. Dev. Neurosci. 10:1-11; Gumpel M., et al. 1987. Ann. New York Acad. Sci. 495:71-85) or myelin-forming cells, such as Schwann cells (Blakemore W. F., 1977. Nature 266:68-9; Blakemore W. F., Crang A. J., 1988. Dev. Neurosci. 10:1-11; Honmou O. et al., 1996. J. Neurosci. 16:3199-208), or olfactory ensheating cells (Franklin R. J. et al., 1996. Glia 17:217-24; Imaizumi T. et al., 1998. J. Neurosci. 18(16):6176-6185; Kato T. et al., 2000. Glia 30:209-218), can elicit remyelination in animal models and recovery of electrophysiological function (Utzschneider D. A. et al., 1994. Proc. Natl. Acad. Sci. USA. 91:53-7; Honmou O. et al., 1996. J. Neurosci. 16:3199-208). It is possible to prepare such cells from patients or other persons for cell therapy. However, this method is considerably problematic because tissue material must be collected from either the brain or nerves.
Neural progenitor cells or stem cells derived from brain have the ability to self-renewal and differentiate into various lineages of neurons and glia cells (Gage F. H. et al., 1995. Proc. Natl. Acad. Sci. USA. 92:11879 83; Lois C., Alvarez-Buylla A., 1993. Proc. Natl. Acad. Sci. USA. 90:2074-7; Morshead C. M. et al., 1994. Neuron 13:1071-82; Reynolds B. A., Weiss S., 1992. Science 255:1707-10).
By transplantation into newborn mouse brain, human neural stem cells collected from fetal tissues differentiate into neurons and astrocytes (Chalmers-Redman R. M. et al., 1997. Neurosci. 76:1121-8; Moyer M. P. et al., 1997. Transplant. Proc. 29:2040-1; Svendsen C. N. et al., 1997. Exp. Neurol. 148:135-46), and myelinate the axons (Flax J. D. et al., 1998. Nat. Biotechnol. 16:1033-9). Remyelination and recovery of impulse conduction upon transplantation of neural progenitor (stem) cells derived from adult human brain into demyelinated rodent spinal cord have been reported (Akiyama Y. et al., 2001. Exp. Neurol.).
These studies have evoked great interest due to the indicated possibility of the application of the above-mentioned cells to regenerative strategy of neurological diseases (Akiyama Y. et al., 2001. Exp. Neurol.; Chalmers-Redman R. M. et al., 1997. Neurosci. 76:1121-8; Moyer M. P. et al., 1997. Transplant. Proc. 29:2040-1; Svendsen C. N. et al., 1997. Exp. Neurol. 148:135-46; Yandava B. D. et al., 1999. Proc. Natl. Acad. Sci. USA. 96:7029-34). However, in order to establish cell transplantation therapy (including autologous transplantation) using these cells, still problems, such as establishment of harvest method and requirement of cell expansion using trophic factors, remain to be solved.
According to the recent studies, neural stem cells were revealed to be able to differentiate or transform into hematopoietic cells in vivo, suggesting that neural progenitor (stem) cells are not restricted to the neural cell lineage (Bjornson C. R. et al., 1999. Science 283:534-7). Furthermore, bone marrow stromal cells (not mesenchymal stem cells in the bone marrow) are reported to differentiate into astrocytes by the injection into the lateral ventricles of neonatal mice (Kopen G. C. et al., Proc. Natl. Acad. Sci. USA. 96:10711-6), and into neurons in vitro when cultured under appropriate cell culture conditions (Woodbury D. et al., 2000. J. Neurosci. Res. 61:364-70).